[unreadable] The detrimental health consequences of childhood obesity are evident in the emergence of "adult" diseases such as pre-diabetes, the metabolic syndrome and type 2 diabetes mellitus in today's youth. Disconcerting is that in adults, each of these conditions is strongly predictive of cardiovascular mortality. Still little is known about the vascular health of obese children and to which extend the early metabolic consequences of adiposity are toxic to the vasculature. Preliminary data by the candidate and recent studies in adults, suggest that exaggerated post-prandial glycemia may be injurious to the vasculature, even in ranges below the diagnostic cut-off for pre-diabetes. Therefore, the overall objective of this proposal is to determine whether increases in meal-stimulated glucose excursions in obese youth are related to physiologic measures and biomarkers of vascular toxicity. The Candidate is a junior faculty member in the Section of Pediatric Endocrionolgy at the Yale University. Her long term career goal is to become an independent investigator in childhood obesity and diabetes with the ultimate goal of impacting the metabolic/cardiovascular consequences of childhood obesity. Yale University's longstanding history in pediatric obesity and diabetes research places the candidate in a strong position to accomplish this task. Dr. Burgert will be mentored by Dr. Sonia Caprio and Dr. William Tamborlane, two highly accomplished investigators in this field, who are all committed to her success. This K-23 application will focus on examining the relationship between post-prandial glucose exposure (as assessed by OGTT and the Medtronic MiniMed continuous glucose monitoring system) and biomarkers of vascular health in a large cohort of non-diabetic obese youth. Non-invasive techniques will be used to assess endothelial function of vasculature such as peripheral arterial tonometry (PAT) and flow mediated vasodilation of the brachial artery FMD). The second aim will determine whether attenuation of postprandial glycemia leads to improvement in cardiovascular risk profile and vascular function. To this end a double blind placebo controlled intervention study with acarbose will be performed in a select group of subjects. Results of such an intervention study will provide important preliminary data for future large-scale treatment studies directed at improving cardiovascular health by reversing early metabolic abnormalities in obese children. [unreadable] [unreadable] [unreadable]